The present invention relates to an apparatus and method for providing x-ray therapy in humans. More specifically, the present invention relates to an apparatus for providing in-situ radiation treatment that utilizes a miniature energy transducer to produce x-rays, wherein the energy transducer includes a Schottky cathode tip.
Restenosis is a heart condition that afflicts 35%-50% of all people who undergo balloon angioplasty to improve blood flow in narrowed sclerotic arteries. The condition consists of a significant re-closing of the treated artery segment hours to several months after the procedure. As a result, the arterial lumen size is decreased and the blood flow downstream from the lesion site is impaired. Consequently, patients afflicted with restenosis must undergo an additional balloon angioplasty, and in some cases a coronary bypass surgery must be performed. Aside from the pain and suffering of these patients, recurrent stenosis is also a serious economic burden on society, with estimated expenses as high as 3.0 billion dollars per year in the United States economy alone.
Attempts to treat restenosis have been concentrated in both the pharmacological and medical device areas. While pharmacological solutions have been proven effective in treating only acute restenosis, a condition developing immediately after balloon angioplasty, some progress has been made with medical devices in the treatment of long term restenosis, a condition that develops up to a few months following balloon angioplasty. An example for such medical device is the stent. Stents can be inserted into an occluded artery to hold it open. Stents have been shown to prevent two of the three mechanisms that cause recurrent stenosis, namely, elastic recoil of the artery and negative remodeling of the arterial structure. The third mechanism, neointimal growth, consists of hyper-proliferation of smooth muscle cells from the lesion into the lumen and is not prevented by stents.
Ionizing radiation holds great promise for treating restenosis. Ionizing radiation serves to damage undesirable hyper-proliferating tissue and ultimately to prevent the hyper-proliferation of smooth muscle cells in the irradiated region. Research has shown that gamma and beta radiation delivered at the location of stenotic lesions effectively stop both animal and human intimal proliferation. The effective, yet non-hazardous, required dose to treat human restenosis is between seven and forty Gray (mjoule/gram), preferably a dosage greater than fifteen Gray measured two mm from the center of the radiation source, which penetrates the artery wall at a two mm depth over the lesion length.
In view of the above, various methods have been proposed to provide ionizing radiation treatment. For example, radiation catheters, based on the use of radioactive sources such as betaxe2x88x92emitting 32P, 90Sr/90Y, 188W/188Re, beta+emitting 48V or gamma emitting 192Ir, are at various stages of development and clinical evaluation. The radioactive sources, in a variety of configurations, are introduced to the treatment sites using special radiation catheters and the radioactive source is placed at the treatment site for a predetermined time period as to deliver the proper radiation dose. Radioactive stents are also used as alternative delivery means, composed of the above radioactive isotopes.
The gamma and beta radioactive sources used by the present radiation catheters and radioactive stents, however, have several drawbacks including a limited ability to provide selective control over the dose distribution or overall radiation intensity, and the logistical, regulatory, and procedural difficulties involved in dealing with radioactive materials. In addition, gamma-emitting devices jeopardize patients by exposing healthy organs to dangerous radiation during the introduction of the radiation source. Hospital personnel that handle radioactive materials are also at risk due to exposure. In addition to the risks these devices impose on patients, hospital staff, and the environment, use of these devices invokes a regulatory burden due to the need to comply with nuclear regulatory requirements.
An additional approach to providing ionizing radiation treatment is through the use of an x-ray emitting energy transducer, which is not radioactive. Conventional x-ray radiation for radiotherapy is produced by high-energy electrons generated and accelerated in a vacuum to impact a metal target. The x-ray emission is directly proportional to the electron beam current. However, the efficiency of x-ray generation is independent of electron current, but rather depends on the atomic number of the target material and on the acceleration voltage. Yet, another method for the production of x-rays is by direct conversion of light into x-ray radiation. It is known that the interaction of light with a target can produce highly energetic x-rays when the power densities achieved are in the range of 1016-1017 watt/cm2. With the development of femtosecond laser, such power densities are achievable with moderate size lasers (See C. Tillman et al, NIMS in Phys. Res. A394 (1997), 387-396 and U.S. Pat. No. 5,606,588 issued to Umstadter et al., the contents of each of which are incorporated herein by reference). A 100 femtosecond , one mJ laser pulse focused down to a 3 micron spot, for example, will reach this power density level.
A variety of medical applications of the direct laser light conversion method of x-ray generation are currently in the development stage. The direct laser light conversion method, for example, has been considered for medical imaging (See, Herrl in K et al. Radiology (USA), vol. 189, no. 1, pp. 65-8, Oct. 1993). Another medical application of femtosecond lasers is in improved non-thermal ablation of neural or eye tissue for surgical purposes (See, F. H. Loesel et al. Appl.Phys.B 66,121-128 (1998)). The development of compact table top models of femtosecond lasers makes laser generated x-rays an attractive alternative for radioactive material based radiotherapy.
Based on the above, an x-ray brachytherapy treatment apparatus and method has been developed. In x-ray brachytherapy an internal x-ray emitting miniature energy transducer generates x-rays in-situ. Co-pending and commonly assigned U.S. Pat. application Ser. No. 09/325,703 filed Jun. 3, 1999, and U.S. patent application Ser. No. 09/434,958 filed Nov. 5, 1999, describe miniaturized energy transducers that are coupled to flexible insertion devices to permit x-ray radiation treatment within the human body. Use of the miniaturized x-ray emitting energy transducer offers certain advantages with respect to intra vascular gamma and beta sources. These advantages are, but are not limited to, localization of radiation to the treatment site so that the treatment site may be irradiated with minimal damage to surrounding healthy tissue; reduction of hospital personnel risk due to exposure to radioactive materials; and minimization of the regulatory burden and additional costs that arise from the need to comply with nuclear regulatory requirements.
A variety of different types of cathode and anode structures have been proposed for the energy transducer. One proposal is to utilize a hollow cathode, which includes a cathode shell that defines a cavity. A light pulse is introduced into the cavity in order to heat an outer surface of the cathode shell, thereby causing thermionic emission of electrons from the outer surface. Another proposal for a hollow cathode incorporates the use of an electron escape nozzle, wherein an ion and electron plasma is generated in the cavity either by applying a light signal to an inner surface of the cathode shell or by providing a spark gap in the cavity of the conducting cathode shell. The electrons exit the cathode shell via the escape nozzle and are accelerated to the anode upon the application of a voltage pulse to the cathode. Still further, in a linear reverse cathode emission type of transducer, an anode is located at a first end of a transducer body and an emission element is located at a second end of the transducer body opposite the anode. The emission element is either a photoemission electron source or a thermionic emission surface, and generates electrons when activated by a light source.
One limitation that the different types of miniature energy transducers described in the above-cited references suffer from is imposed by their mode of operation, which involves the use of pulsed voltage. While replacing direct current (DC) voltage with pulse voltage increases the miniature x-ray transducer surface flashover threshold, thus enabling the manufacturing of smaller length devices, it holds some disadvantages. Pulsed voltage generators are more expensive, involve additional technological complexity and are less reliable when compared to DC voltage power suppliers. However, miniature x-ray transducers that are applied with a DC voltage in order to accelerate the emitted electrons from the cathode to the anode are facing efficiency problems. Taking into account the relatively low current density that can be produced with field emission cathodes supplied with DC voltage (in orders of milliamperes/mm2 at most) it is questionable whether a miniature x-ray transducer with a cold cathode, can deliver the relevant x-ray dose for restenosis treatment. Miniature energy transducers that include a heated filament (thermionic) cathode also suffer from low electron generation efficiency while generating excessive heat.
One method to increase the current densities generated by miniature x-ray transducers supplied with DC voltage is the incorporation of both thermionic and field emission mechanisms in a single cathode. This type of emission is known as Schottky emission. Schottky emission is generated by heating a Schottky cathode tip to approximately 1,500xc2x0 C. prior to its exposure to an electrical field created in the gap between a cathode and an anode. Providing thermal energy to the Schottky cathode tip increases the probability for electron emission due to xe2x80x9ctunneling effectxe2x80x9d. This means that the probability of electrons replenished from the cathode surface to be accelerated towards the anode, following the voltage gradient to which they are exposed, is increased. Using a low work function material as an electron source further increases this probability. Thus, current densities obtained are orders of magnitude higher than with field emission mechanism alone (in orders of hundreds of milliamperes/mm2), enabling the delivery of the relevant x-ray dose for restenosis treatment.
General information regarding Schottky cathode structures and Schottky emission can be found in the following references: C. H. Hinrichs, W. A. Mackie, P. A. Pincosy and P. Poulsen, xe2x80x9cThe Extended Schottky Cathodexe2x80x9d, IEEE Transactions On Electron Devices, Vol. 37, No. 12, December 1990, pp. 2575-2580, the contents of which is incorporated herein by reference; and L. W. Swanson and G. A. Schwind, xe2x80x9cA Review of the ZrO/W Schottky Cathodexe2x80x9d in xe2x80x9cHandbook of Charged Particle Opticsxe2x80x9d by Jon Orloff (Editor), CRC Press, June 1997, pp.77-102, the contents of which is incorporated herein by reference.
Accordingly, it is an object of the present invention to provide a miniature energy transducer utilizing a Schottky cathode tip structure that combines both thermionic and field emission mechanisms in order to increase the current densities generated by the miniature energy transducer and provide the relevant therapeutic dose for restenosis treatment.
The present invention provides an apparatus for providing in-situ radiation treatment that utilizes a miniature energy transducer to produce x-rays, wherein the energy transducer includes a Schottky cathode. More specifically, the energy transducer includes a transducer body, an anode provided at a first end of the transducer body, and a cathode provided at a second end of the transducer body opposite the anode. The energy transducer is coupled to an energy source by a flexible insertion device. The energy source provides electrical and/or light signals to the energy transducer via the flexible insertion device. In one preferred embodiment, the anode includes a hollow central core, wherein an optical fiber is provided in the hollow central core. Light transmitted from the energy source to the energy transducer by the flexible insertion device is focused on a Schottky cathode tip of the cathode by the optical fiber provided in the hollow core of the anode. The application of the light signal to the cathode tip results in heating of the cathode and along with the electric field generated by the acceleration voltage it leads to electron Schottky emission and electron acceleration towards the anode. In another preferred embodiment, an electrical current, transmitted from the energy source to the energy transducer by the flexible insertion device, is applied to the Schottky cathode, causing thermo-emission. The electrons generated due to this process are accelerated towards the anode across a voltage difference between the anode and the cathode. The Schottky cathode tip is made from a low work function material, preferably selected from the group consisting of: tungsten, thoriated tungsten, lanthanum hexaboride, and zirconium oxide. The outer diameter of the energy transducer is 1.7 mm or less, while its length is preferably 7 mm or less and most preferably 3 mm or less.